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Citations to this article

MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury
Nicolas Deroide, … , Nathalie Kubis, Ziad Mallat
Nicolas Deroide, … , Nathalie Kubis, Ziad Mallat
Published February 1, 2013
Citation Information: J Clin Invest. 2013;123(3):1176-1181. https://doi.org/10.1172/JCI65167.
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Brief Report Inflammation Article has an altmetric score of 10

MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury

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Abstract

Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell–induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β3 and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

Authors

Nicolas Deroide, Xuan Li, Dominique Lerouet, Emily Van Vré, Lauren Baker, James Harrison, Marine Poittevin, Leanne Masters, Lina Nih, Isabelle Margaill, Yoichiro Iwakura, Bernhard Ryffel, Marc Pocard, Alain Tedgui, Nathalie Kubis, Ziad Mallat

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 4 2 5 10 8 4 5 8 5 5 10 7 3 1 77
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